Dehydrogenation and cyclization of amines



United States Patent O 3,463,781 DEHYDROGENATION AND CYCLIZATION OF AMINES William Hamilton Bell and John Dewing, Runcorn, England, assignors to Imperial Chemical Industries Limited, London, England, a corporation of Great Britain No Drawing. Filed Feb. 28, 1966, Ser. No. 530,338 Claims priority, application Great Britain, Mar. 19, 1965, 11,769/65; May 27, 1965, 22,587/ 65 Int. Cl. C07d 31/04 U.S. Cl. 260-290 11 Claims ABSTRACT OF THE DISCLOSURE A process for the production of pyridine or a hydrocarbyl-substituted pyridine, wherein an aliphatic, nitrogen-containing compound, particularly a primary or secondary amine, or an imine, containing at least five carbon atoms, is dehydrogenated and cyclized by heating with iodine in the vapor phase, in the presence of molecular oxygen and an alkali or alkaline-earth metal compound, preferably together with compounds of silver and/or rare-earth metals such as didymium, and of transition metals such as iron. An advantage of the process is that it permits the eifective use of relatively small quantities of iodine.

This invention is a modification in or an improvement to the invention described in copending application S.N. 515,204, filed Dec. 20, 1965. The said application relates to the dehydrogenation of nitrogenous compounds to form aromatic heterocyclic compounds containing nitrogen in the ring and especially to the dehydrogenation and cyclization of open chain compounds to form pyri dine or substituted derivatives thereof.

The present invention provides a vapour phase dehydrogenation process for the production of aromatic compounds having nitrogen in the ring which comprises heating a halogen with an aliphatic nitrogenous compound containing a sufficient number of carbon, nitrogen and hydrogen atoms in an appropriate arrangement to form the aromatic compound after dehydrogenation in the presence of oxygen and a catalyst comprising a compound of an alkali or alkaline earth metal.

Within the term aliphatic we wish to include open chain aliphatic and alicyclic compounds containing nitrogen in the ring, i.e. compounds which are saturated or only partially unsaturated thus permitting dehydrogenation to an aromatic compound. We do not wish to exclude the possibility of aromatic substituents being attached to the aliphatic part of such a compound. A pre ferred halogen is iodine. Within the terms halogen and iodine we wish to include cases in which the halogen or iodine are formed in situ, e.g. sources of iodine which yield iodine under the reaction conditions.

The process of the present invention is especially applicable to the dehydrogenation of aliphatic nitrogenous compounds containing an open chain of carbon and nitrogen atoms, appropriate atoms in the chain having sufficient hydrogen atoms to permit cyclization to occur on dehydrogenation to form the aromatic compound. Thus preferred starting materials are exemplified by primary and secondary amines and imines having hydrogen atoms on the carbon or nitrogen atoms which take part in the formation of the cyclizing bond. Compounds such as nitriles and isonitriles having five carbon atoms and no hydrogen atoms on the terminal carbon or nitrogen atom do not readily undergo cyclization.

An appropriate starting material for any given product will be readily ascertainable by one skilled in the art from a knowledge of the structure of the desired product. Thus if the starting material contains one nitrogen atom then the product will usually be pyridine or a substituted 3,463,781 Patented Aug. 26, 1969 derivative thereof. Simple starting materials with only five carbon atoms, one nitrogen atom and a sufllcient number of hydrogen atoms will form pyridine itself. More complex starting materials will form substituted derivatives of pyridine. Preferably the nitrogen atom is bonded to not more than two carbon atoms, since this eliminates the need for a cracking type reaction to occur or some rearrangement of groups around the nitrogen atom. Suitable substituents which lead to the production of substituted pyridines may include for example, alkyl, halogen, hydroxyl or pyridyl radicals or combinations of these. Using isopropylidene propylamine for example, a-picoline is obtained and using appropriately substituted starting materials, compounds of the quinoline, isoquinoline or bipyridyl series may be obtained. Depending upon the conditions used for the reaction however the substituent itself may undergo change for example dehydrogenation (e.g. an ethyl group may be converted to a vinyl group), or may be removed by a cracking reaction. As will be apparent, the starting compounds used herein may also be defined as primary, secondary or tertiary alkyl amines or alkyl alkylidene amines wherein the amines have at least 5 carbon atoms and each alkyl or alkylidene group therein has no more than 5 carbon atoms.

The starting materials may be formed in situ from suitable simpler precursors which together provide the required structure to form the aromatic heterocyclic compound after combination and dehydrogenation. Examples are provided by the use of aliphatic aldehydes and primary amines which condense to form imines, e.g. acetaldehyde and propylamine which. form ethylidene propylamine. Higher yields are obtained if the precursors are mixed before reacting with iodine although some desired product may be formed it the precursors and iodine are mixed together in the reaction vessel.

Temperatures should be high enough to maintain the reactants in the gaseous phase. Temperatures in the range 300 C. to 800 C. and preferably 350 C. to 650 C. are convenient. Outside this range yields decrease and difiiculties may be encountered with clogging of the apparatus or undesired side reactions.

The alkali or alkaline earth metal may be present as a solid, preferably carried on a support material, or it may be used in the molten form.

Oxygen may be present as air, as pure oxygen or as any other convenient source of oxygen.

Especially suitable alkali metals are lithium and potassium.

In addition to the alkali metal or alkaline earth metal the catalyst preferably comprises a compound of silver and/ or rare earth metals including scandium and yttrium. Compounds of the mixture of rare earth metals known as didymium may conveniently be used. Didymium oxide for example has approximately the following composition, 45% La O 38% Nd O 11% Pr O 4% Sm O and 2% residuals. Compounds of transition group metals may also be present. By transition group metal We mean a metal having an atomic number within the ranges 22-29, 40-46, 72-79 and 82-84 all inclusive. A preferred transition metal is iron.

Mixtures of more than one member of each class may be used. A wide variety of compounds may be used but the halides are convenient. The catalyst is preferably supported on a carrier. The carrier should preferably have a high ratio of surface area to weight. Examples of carriers are a-alumina, silica or pumice.

The ratio of iodine to starting material may vary within wide limits. Owing to the high cost of iodine it is desirable to use as small an amount of iodine as is consistent with an acceptable yield of product. One advantage of thepresent invention is that the dehydrogenation may be carried out in the presence of only very small amounts of iodine, for example between 0.01 to 0.3 mole per mole of starting material, or lower or higher if desired.

The amount of oxygen required depends in general on in by a mixed stream of nitrogen and oxygen, the nitrogen and oxygen flow rates being varied so as to vary the mole ratios of iodine and oxygen to propylidene ethylamine. The nitrogen/iodine flow rate was about 20 litres/hour and oxygen/iodine about 4 litres/hour giving a total gas the compound being dehydrogenated. Approximately flow of about 38 litres/hour. stoichiometric amounts of oxygen may be used in ac- The outgoing gas stream from the reactor was passed cordance with the number of hydrogen atoms which are through a heated tube, with a gas sampling point for gas in theory to be removed from the compound and oxidised liquid chromatography analysis, and then through a conto water. For example, 1 mole of ethylidene propylamine denser. The products were collected in two flasks of distheoretically requires 1.5 moles of oxygen for the contilled water. version into pyridine. In practice 0.5 to 1.5 Of the The aqueous solution with washings of condenser etc., theoretical amount is conveniently used but this can be was analysed for pyridine by u.v. Yields of pyridine on lower or higher as required. propylidene ethylamine were determined.

Residence times of reactants in the reaction zone are o A L convenlently within the range 0.01 to seconds. At 500 EX ES 1 9 C. times of 01-10 seconds are suitable but optimum These examples were deslgned to explore the effect of times will depend upon temperature and other factors. variation in catalyst composition. Detalls are listed in Examples of the invention will now be described. Table I.

TABLE I Partial 19551118 Catalyst composition Mole ratios starting material Ex. No. Support Gm./100 gm. support I2/PE O2/PE mm Yield 1 0.11120 KBr 2.0a D101 1.09 AgI 1.02 0.12 1.05 76 28.6 2 A120. KBr 6.0 D1011 6.5 .AgI 3.06 0.18 1. 42 59 3 1205 KBr 6.0 DiCl; 6.5 AgI3 0.10 1. 24 e4 37 4... 111205 E31 00 DiCl 1.0 AgI3 0.13 1.20 as 33.6 5 111205 KBr 0.0 D101; 6.5 AgI 1 0. 09 1. 26 04 35.8 e- 111.05 KBr 2.0 D101 6.5 .AgI3 0.09 1. 24 62 32.5 7- 0.11.120, KBr 0.0 0.12 1.0 79 24.0 s 0.111105 K131 6.0 D101 6.5 0.15 1.15 06 20.2 0- (1.1120. KBr 0.0 AgI3 0.17 1.41 54 23.5

The reactor was a quartz tube of total length 2 ft, with a preheat section of length 8 ins. The volume of the EXAMPLES 10-14 These examples were designed to show the effect of reactor was approximately 200 mls. and of the catalyst 35 various support materials. Results are given for a and 7 approximately 100 mls. Propylidene ethylamine and A1 0 alone for comparison. Details are listed in Table II.

TABLE II Partial pressure Catalyst composition Mole ratios starting material, Support Gm./100 gm. support Iz/PE Oz/PE mm. Yield aAlzOa KBr 6.0 D1011 6.5 .AgI 0. 18 1.42 59 35 .4110 KBr 6 0 D1013 6.5 .AgI 0. 10 1. 24 64 37 S103 KBr 6 0 DiCl 6.5 AgI 0. 18 1. 5 52. 6 32.6 Pumice KBr 6 0 D101 6.5 AgI 0. 12 1. 05 75 30. 6 7x120. alone 0.11 0. 90 89 20.8 S102 chips F0 0 7 5 LiOH 0.4 0. 15 1. 2 64 35. 6 1141 0 alone 0. 14 0. 87 89 21. 2

iodine were passed separately through the preheat section and mixed at the reaction temperature.

EXAMPLES 15-19 These examples were designed to show the effect of The whole reactor was heated in a furnace to 500 C. lithium compounds supported on Ill-A1203. Details are Residence time was 3.2 secs. Propylidene ethylamine was listed in Table HI.

TABLE III Mole ratios Partial Catalyst composition, pressure,

gm./100 gm. support Iz/PE Oz/PE mm. Yield 0. 13 1. 0 76 35 0. 13 1. 06 71 35. 7 l 0. 14 1. 05 24. 6 6.5 D1013 0. 07 0. 25. 3 3.0 AgI 0.12 1.0 76 25. 0

carried into the reactor by bubbling a stream of nitrogen 60 EXAMPLES 20-28 These examples were designed to show the elfect of various transition metals. Catalysts were supported on a-Al O Details are listed in Table IV.

TABLE IV Mole ratios Partial Catalyst composition, pressure,

gm./10l) gm. support Ig/PE OzIPE PE, mm. Yield KBr 6.0 D1013 6.5 AgI 3.0 0. 18 1. 42 59 35. 1 KB! 6.0 D101 6.5 (NH4)2M0O4 2.6 0.13 1. 03 74 24. 8 KBI 6.0 D101 6.6 MHIziHzO 5.0 0. 14 1.46 66 26. 4 KB! 6.0 D1013 6.5 COIz2H2O 4.6 0.13 1.12 69 26. 3 KB! 6.0 DiCla 6.5 FeIz4HzO 5.0 0.14 1. 15 67 31.8 KBr 6.0 D101 6.5 Ni(NO 6HO 3.8 0.15 1. 21 63 24. 4 KB! 6.0 D101 6.5 CuCl22HzO 2.3 0.14 1.16 68 27 KBr 6.0 D101 6.5 CrChQHZO 5.3 0.15 1. 55 65 27.4 .0 DiClz 6.5 Coll/I004 2.9 0. 12 1.01 76 27. 3

5 EXAMPLE 29 A catalyst was prepared consisting of 2.08 parts potassium bromide, 1.09 parts didymium chloride, 1.02 parts silver iodide on 100 parts of alumina. The alumina pellets of A2 in. diameter were calcined at 900 C. for 24 hours before precipitation of the catalyst. The alumina was impregnated with an aqueous solution containing the catalyst components in the form of soluble salts. Insoluble catalysts were formed on the carrier by treatment with a suitable reagent. For example silver iodide was formed by reacting silver nitrate with hydriodic acid. The impregnated carrier was dried on a steam bath with continuous stirring and subsequently in a furnace at 550 C. for 5 hours.

100 grams of the above catalyst were loaded into a quartz reactor. Ethylidenepropylamine (1.8 gm.) entrained in 1.87 litres of nitrogen, iodine (0.73 gms.) entrained in 2.53 litres of air and steam (1.59 litres) were passed over the catalyst at 500 C. over a period of 8 minutes. The reactants were passed into the reactor separately and the iodine and ethylidenepropylamine were mixed immediately before passing over the catalyst. This gave a yield of 0.245 gins. pyridine (14.7%) as shown by gas liquid chromatography and ultra-violet spectroscopy.

EXAMPLE 3 A catalyst was prepared consisting of 2.08 parts potassium bromide, 1.09 parts didymium chloride, 1.02 parts silver iodide on 100 parts of pumice (22-30 mesh). The pumice was impregnated with an aqueous solution containing the catalyst components in the form of soluble salts. Insoluble catalysts were formed on the carrier by treatment with a suitable reagent. For example silver iodide was formed by reacting silver nitrate with hydriodic acid. The impregnated carrier was dried on a steam bath with continuous stirring and subsequently in a furnace at 550 C. for hours.

100 grams of the above catalyst were loaded into a quartz reactor. 5.8 grams of acetaldehyde entrained in nitrogen, 5.44 grams of propylamine entrained in nitrogen, 2.75 grams, of iodine entrained in air and steam were passed over the catalyst at 500 over a period of 30 minutes. The acetaldehyde and propylamine streams were premixed at room temperature and these and the other reactants were passed into the reactor separately and mixed immediately before passing over the catalyst. The flow rate of the air iodine mixture was 19 litres per hour, of the acetaldehyde/nitrogen mixture 8.5 litres per hour, of the propylamine nitrogen mixture 30 litres per hour and/ or the steam 11.9 litres per hour. 1.13 grams of pyridine were obtained (as shown by gas liquid chromatography and ultra-violet spectroscopy) representing a percentage yield of pyridine based on propylamine of 15.5.

Although the invention has been illustrated by the above examples it is not limited thereto and is applicable to a wide range of starting materials having between them a chain of 5 carbon atoms and a nitrogen atom. Examples of such compounds will be found in the above mentioned Serial No. 515,204. A wide variation in the composition of the catalyst is also possible and the example is intended merely to be illustrative of a large class of catalytic compounds within the scope of the claims.

What we claim is:

1. In a process for the preparation of pyridine or a hydrocarbyl-substituted pyridine wherein an amine selected from the group consisting of primary, secondary and tertiary alkyl amines and alkyl alkylidene amines, wherein said amines have at least 5 carbon atoms and wherein each alkyl or alkylidene group therein has no more than 5 carbon atoms, is heated with iodine in the vapor phase at a temperature in the range of from 300 C. to 800 C., the improvement wherein said amine is heated in the presence of oxygen and a catalyst consisting essentially of an alkali metal or alkaline earth metal salt selected from the group consisting of the halides, hydroxides and carbonates.

2. A process as claimed in claim 1 in which the amine is a primary or secondary alkyl amine or an alkyl alkylidene amine derivable by condensation of an aldehyde with a primary amine.

3. A process as claimed in claim 1 in which the alkali metal is lithium.

4. A process as claimed in claim 1 in which the alkali metal is potassium.

5. A process as claimed in claim 1 in which the catalyst also includes at least one member of the group consisting of silver halides and the rare-earth metal halides.

6. A process as claimed in claim 5 in which the catalyst includes a didymium halide, wherein the didymium is composed of a mixture of the rare-earth metals La, Nd, Pr and Srn.

7. A process as claimed in claim 5 in which the catalyst also includes at least one transition metal halide selected from the elements having an atomic number within the range 22 through 29, 40 through 46, 72 through 79, and 82 through 84.

8. A process as claimed in claim 7 in which the transition metal halide is an iron halide.

9. A process as claimed in claim 8 wherein said metal is present as a halide thereof.

10. A process as claimed in claim 1 in which the catalyst is supported on alumina, silica, or pumice.

11. A process according to claim 1 wherein the product is pyridine, the amine starting material is propylidene ethylamine, the catalyst is a supported catalyst consisting essentially of potassium bromide, didymium chloride and silver iodide, the amount of iodine is between 0.01 to 0.3 mole per mol of propylidene ethylamine and the amount of oxygen is approximately stoichiometric.

References Cited Kirk-Othmer, Encyclopedia of Chemical Technology (Wile, N.Y., 1964) vol. 4, p. 843.

Smith, The Chem. of Open-Chain N Cpds (Benjamin, N.Y., 1965), vol. 1, pp. 50-51.

HENRY R. JILES, Primary Examiner C. M. SHURKO, Assistant Examiner US. (:1. X.R. 

